Hemorrhage resulting from traumatic injuries is a major cause of death in accidents, and the primary cause of death on the battlefield. Early and effective hemorrhage control can save more lives than any other measure. Tissue adhesives and sealants have been developed to control bleeding; but, currently, all existing haemostatic agents for abdominal intracavitary bleeding are designed to be used in the operating room--not in an emergency at the site of accident or in the battlefield. The goal of the proposed project is to develop an intracavitary hemostatic agent --Hemostatic Adhesive Foam (HAF) --that promotes hemostasis in cases of severe bleeding that would otherwise lead to exsanguination. This approach is based on the physical and coagulation properties of a mixture of Teleostan Gelatin type A, Polyvinylpyrrolidone, Sucrose and Fibrinogen, with a water-soluble foam inducer; the addition of thrombin and P-selectin inmunoglobin chimera, and on its form of application. The cross- linked compound forms an adhesive matrix over damaged, lacerated tissue following abdominal or other intracavitary trauma. In preliminary studies, it was demonstrated that HAF can generate adaptable foam that is distributed uniformly, and adheres to the abdominal cavity, even under profuse bleeding, when it is injected intraperitoneally through a Verres disposable needle. Our hypothesis is that once HAF is injected in the peritoneal cavity, it distributes and adheres evenly to the walls, improving the adhesiveness between lacerated tissues and potentiating clot formation through the up-regulation of P-selectin. Our specific aims are to demonstrate in two ex vivo models: a) that the upregulation of P-selectin enhances the adhesive, physical, and coagulation properties of HAF, and to determine the extent to which this agent promotes adhesiveness between tissue and damaged surfaces in the presence of profuse bleeding; b) its effects on clot formation; c) to determine if the addition of other thrombin and fibrin like agents and P-selectin-immunoglobulin chimera -that specifically stimulate P-selectin, will enhance clot formation and clot strength effects of this agent, and; d) evaluate restoration of vital functions and survival. Phase I proposed studies could provide the "proof of concept" for the use HAF as an intracavitary hemostatic agent in cases of non-compressible hemorrhage. Phase II studies will define the adhesive and coagulation properties of the compound in an intracavitary hemorrhage military-relevant animal model (pig), study tissue distribution, pharmacokinetics, reabsorption and toxicity of HAF. Upon completion of the phase II effort, phase III studies will involve extended pharmacokinetic studies for filing an Investigative New Drug (IND) application to start studies in human volunteers. In an age of speed, civil violence and armed conflicts, the incidence of penetrating and blunt injuries to the abdomen has been on the increase. On average, nationwide 41.8% of the trauma cases admitted at hospitals are due to road traffic accidents. Also, hemorrhage remains the primary cause of death on the battlefield in conventional warfare. Although, the morbidity and mortality from these injuries are gradually decreasing, abdominal injuries still pose a formidable problem, especially in young adults, Early and effective hemorrhage control could theoretically save more lives than any other measure; however, the best strategy to achieve this goal outside of the operating room and particularly in austere and hostile field situations is not clear. Currently, all existing haemostatic agents for abdominal intracavitary bleeding are designed to be used in the OPERATING ROOM not at the site of injury (i.e. battlefield, car accident, shot wound). A novel form of application through a Verres needle and the utilization of novel procoagulants compounds such as P-selectin immunoglobulin chimera incorporated to gelatin sealants could provide the adhesion strength and coagulatory properties necessary to stop bleeding in the site of injury We propose to develop an intracavitary hemostatic agent --Hemostatic Adhesive Foam (HAF)--that forms an adhesive matrix over damaged, lacerated tissue following abdominal or other intracavitary trauma to promote hemostasis in cases of severe bleeding which, if not treated immediately, would lead to exsanguinations. The proposed study provides an opportunity to demonstrate HAF efficacy as an intracavity hemostatic agent. This therapeutic approach will reduce killed in action (KIA) rate, increased life saving capability for the medic, and reduce need for surgery and transfusion. [unreadable] [unreadable] [unreadable]